1. Field of the Invention
The present invention relates to radioisotopes and to radiographic techniques for detecting tumors, and particularly to a cancer-imaging agent and a method of radioimaging using the same, and more particularly to a method of detecting cancer by monitoring choline uptake using choline radiolabeled with technetium-99m (99mTc).
2. Description of the Related Art
There is presently great interest in methods for the noninvasive diagnosis of a variety of diseases, such as cancer. Radiopharmaceuticals formed from gamma-ray emitting radionuclide-labeled biologically active molecules are presently being studied. The biologically active molecules serve to localize the radionuclides at the sites of disease, and thus allow the sites to be visualized by gamma scintigraphy. The molecules are typically proteins, antibodies, antibody fragments, peptides or polypeptides, or peptidomimetics. The molecules interact with a receptor or binding site expressed at the sites of the disease, or with a receptor or binding site on an endogenous blood component, such as platelets and leukocytes, that accumulate at the sites. This interaction results in selective localization of a percentage of the injected radiopharmaceutical, while the remainder is cleared either through the renal or hepatobiliary systems.
The localized radiopharmaceutical is then imaged externally using gamma scintigraphy. The relative rates of sequestration, clearance and radionuclidic decay determine the ease of visualization, often expressed as the target-to-background ratio. Frequently, only certain portions of the biologically active molecules bind to the receptors. These portions are termed the recognition sequences or units.
There are two general methods for labeling biologically active molecules with radionuclides for use as radiopharmaceuticals, which are generally termed direct and indirect labeling. Direct labeling involves attaching the radionuclide to atoms on the biologically active molecule, while the indirect method involves attaching the radionuclide via a chelator. The chelator can either be attached to the biologically active molecule prior to reaction with the radionuclide, or the radionuclide-labeled chelator moiety can be attached to the biologically active molecule.
A number of radiopharmaceuticals formed from radionuclide-labeled proteins, antibodies or antibody fragments are being investigated. However few are actually being used clinically. The infrequent use of such compounds is due to a combination of factors that make developing these radiopharmaceuticals difficult, including problems with manufacturing and quality control, non-optimal sequestration and clearance rates, and the occurrence of antigenic or allergic responses to the radiopharmaceuticals. These problems are mainly due to the macromolecular nature of the proteins, antibodies and antibody fragments. Their high molecular weight makes direct chemical synthesis impractical. Therefore, they must be synthesized by recombinant or cloning techniques that typically give low yields and require extensive isolation and purification procedures. Their molecular weight can slow their rates of localization and preclude their clearance by an active elimination mechanism via the kidneys or liver, resulting in prolonged retention in the circulation, which causes a high background level during imaging. Also, the body's immune system tends to recognize more efficiently larger exogenous species.
The use of lower molecular weight molecules with known high-uptake rates, particularly in cancer cells, can alleviate these problems. It would be desirable to provide such a radioimaging agent. Thus, a cancer-imaging agent and method of radioimaging using the same solving the aforementioned problems is desired.